Cancer is a disease resulting from an abnormal growth of tissue. Certain cancers have the potential to invade into local tissues and also metastasize to distant organs. This disease can develop in a wide variety of different organs, tissues and cell types. Therefore, the term “cancer” refers to a collection of over a thousand different diseases.
Anaplastic lymphoma kinase (ALK), a member of the insulin receptor superfamily of receptor tyrosine kinases, has been implicated in oncogenesis in hematopoietic and non-hematopoietic tumors. The aberrant expression of full-length ALK receptor proteins has been reported in neuroblastomas and glioblastomas; and ALK fusion proteins have occurred in anaplastic large cell lymphoma. The study of ALK fusion proteins has also raised the possibility of new therapeutic treatments for patients with ALK-positive malignancies. (Pulford et al., Cell. Mol. Life Sci. 61:2939-2953 (2004)).
Insulin-like growth factor (IGF-1) signaling is highly implicated in cancer, with the IGF-1 receptor (IGF-1R) as the predominating factor. IGR-1R is important for tumor transformation and survival of malignant cells, but is only partially involved in normal cell growth. Targeting of IGF-1R has been suggested to be a promising option for cancer therapy. (Larsson et al., Br. J. Cancer 92:2097-2101 (2005)).
ROS1, V-ros Avian UR2 Sarcoma Virus Oncogene Homolog 1 (also known as ROS) is highly expressed in a variety of tumor cell lines. ROS1 is currently an orphan receptor tyrosine kinase whose kinase domain is mostly related to ALK. ROS1 is highly expressed in a variety of tumor cell lines. ROS1 fusion proteins resulting from genetic aberrations have been found in lung cancer and in certain glioblastoma cell lines (Rikova K. et al Cell 131:1190 (2007); Sharma S. Et al Oncogene Res. 5: 91 (1989)). Aberrant expression of ROS1 has been reported in glioma (Watkins D. et al Cancer Genet Cytogenet. 1994 72:130 (1994)). ROS1 kinase inhibitors may be able to block growth of the tumors driven by ROS1 fusions or aberrant expression or activation.
Despite advancements in the art, there remains a need for cancer treatments and anti-cancer compounds.